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CAR T-cell Therapy

IDE196 Combinations for Solid Tumors

Phase 1 & 2

Recruiting

Research Sponsored by IDEAYA Biosciences

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient must be ≥18 years of age

History of syncope

Must not have

Prior treatment with a MEK inhibitor (for Binimetinib Combination)

Concurrent neuromuscular disorders that are associated with elevated creatine phosphokinase (CPK) (for Binimetinib Combination)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approx. 48 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety and effectiveness of a new drug, IDE196, for patients with solid tumors that have a specific gene mutation. The trial has three parts. First, they will test different doses of the drug to see what is safe and what the side effects are. Second, they will test the drug combination with binimetinib to see if it is effective and has any new side effects. Third, they will test the drug combination with crizotinib to see if it is effective and has any new side effects.

Who is the study for?

This trial is for adults with certain solid tumors, including metastatic uveal melanoma, skin cancer, and colorectal cancer that have specific genetic mutations or fusions. Participants must have had prior treatment with a MEK inhibitor (except for Binimetinib Combination), measurable disease, good performance status (ECOG ≤1), life expectancy over 3 months, adequate organ function and cardiac function (for Binimetinib Combination), and agree to use contraception. Exclusions include symptomatic brain metastases, pregnancy/breastfeeding women, recent thromboembolic events or surgeries.

What is being tested?

The study tests the safety and effectiveness of IDE196 alone or in combination with Crizotinib or Binimetinib in patients whose tumors have GNAQ/11 mutations or PRKC fusions. It includes dose escalation to find the right amount of drug and then expands to more patients at this dose. The effects of food on IDE196's absorption are also studied.

What are the potential side effects?

Potential side effects may include issues related to liver function changes due to IDE196; heart problems from Binimetinib; lung issues like pneumonitis from both drugs; vision changes such as retinal vein occlusion from Binimetinib; muscle pain/inflammation due to elevated CPK levels from Binimetinib.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I have a history of fainting.

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I have spinal cord compression.

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I have melanoma or another solid tumor with a specific mutation and it has worsened after treatment.

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My heart pumps well, with an ejection fraction of 50% or higher.

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I can perform daily activities with minimal help and am expected to live more than 3 months.

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I have had pneumonitis or lung disease affecting the tissue and space around the air sacs.

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I finished any previous cancer treatments or major surgeries at least 4 weeks ago.

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I have been treated with a MEK inhibitor before.

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I have a history of lung scarring or fibrosis.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have previously been treated with a MEK inhibitor.

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I have a muscle disorder that increases my CPK levels.

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I have a history of fainting.

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I am not on any medications that can't be stopped for the study.

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I have had surgery to remove my stomach or part of my upper bowel, or I have another significant digestive system condition.

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My tumor is MSI-H/dMMR and I haven't had immune checkpoint inhibitors.

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I do not have AIDS, hepatitis B, or hepatitis C.

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I have brain metastases that are causing symptoms.

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I have been treated with a PKC inhibitor before.

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I still have side effects from previous cancer treatments.

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I am not allergic to mammalian meat products or gelatin.

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My high blood pressure is not controlled by medication.

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I have a history of fainting.

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I have spinal cord compression.

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I have no history or current signs of retinal vein occlusion.

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I am not allergic to binimetinib or its components.

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I have received treatments targeting ALK, MET, or ROS1.

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I have a history of lung scarring or fibrosis.

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I have had pneumonitis or lung disease.

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My heart does not function properly.

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I am not pregnant or breastfeeding.

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I am currently being treated for an infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approx. 48 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approx. 48 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and approx. 48 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose-limiting Toxicity (DLT)

Duration of Response for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee

Maximum Tolerated Dose (MTD)

+5 more

Secondary study objectives

Disease Control by Investigator

Duration of Response by Investigator

Duration of Response for combination with Binimetinib or in combination with Crizotinib in Dose Escalation and in all combination cohorts by Blinded Independent Review Committee

+4 more

Other study objectives

Overall Survival

Progression-Free Survival

Reduction in tumor burden by total volumetric measurement

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: PK Substudy with Pravastatin (OBTP1B1 Substrate)Experimental Treatment1 Intervention

A PK substudy with approximately 18 patients will be nested within the IDE196 and crizotinib combination expansion cohort to evaluate the impact on the pravastatin PK profile by the steady state exposures of IDE196.

Group II: Dose Optimization Crizotinib CombinationExperimental Treatment2 Interventions

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

Group III: Dose Expansion MonotherapyExperimental Treatment1 Intervention

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)

Group IV: Dose Expansion Crizotinib CombinationExperimental Treatment2 Interventions

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) Previously treated MUM, Treatment naïve MUM, MUM patients with human leukocyte antigen (HLA)-A\*02:01 positive status

Group V: Dose Expansion Binimetinib CombinationExperimental Treatment2 Interventions

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)

Group VI: Dose Escalation MonotherapyExperimental Treatment1 Intervention

IDE196 dosed orally, twice daily (BID) for each 28-day cycle

Group VII: Dose Escalation Crizotinib CombinationExperimental Treatment2 Interventions

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

Group VIII: Dose Escalation Binimetinib CombinationExperimental Treatment2 Interventions

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle

Group IX: Crizotinib Monotherapy with Crossover to CombinationExperimental Treatment2 Interventions

Crizotinib dosed orally, twice daily (BID) for each 28-day cycle until disease progression then IDE196 added and dosed orally, twice daily (BID) for each 28-day cycle

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Crizotinib

2014

Completed Phase 3

~2960

Binimetinib

2018

Completed Phase 3

~1250